CHOLINERGIC AND H1-RECEPTOR INFLUENCES OF HISTAMINE ON SLOWLY ADAPTING PULMONARY STRETCH-RECEPTOR ACTIVITY IN THE RABBIT

Afferent impulses of slowly adapting pulmonary stretch receptors (SARs) were obtained by dissecting fine slips from the left vagus nerve (LVN) and by leaving the rest of the nerve intact. In the same SAR preparation, changes of the receptor activity in response to right atrial injections of histamine (10 and 60 mug/kg) were successively examined before and after atropine (1 mg/kg), partial vagal efferent ablation, and mequitazine (1 mg/kg) in 10 rabbits. Administration of histamine led to an increase in the SAR activity, and this effect became more pronounced by increasing the dose of histamine. Atropine treatment diminished the responses of SARs to histamine at different doses. Partial vagal efferent ablation produced by denervation of the rest of the intact LVN slightly reduced the response of SARs to histamine at 10 mug/kg but had no significant effect on the SAR response to 60 mug/kg histamine. In the absence of vagal afferent and efferent activities on the left side, mequitazine, a potent H-1-receptor blocker, completely blocked low- and high-dose effects of histamine on SARs. We compared the responses of the receptor activity to aerosol histamine (1 and 4%) and to topical application of histamine (0.1 ml, 0.025% and 0.1%) in six SAR preparations. The magnitude and duration of increased SAR activity became more prominent by increasing the concentration of histamine. The firing pattern and discharge rate of SARs following aerosol or intratracheal administration of histamine were similar to those after intra-atrial histamine. In addition, we also examined the excitatory responses of SAR activity to right atrial injections of histamine at 10 and 60 mug/kg before and after topical administration of atropine (0.1 ml, 1%, n = 6) or mequitazine (0.1 ml, 1%, n = 6) in 12 SAR preparations. Intratracheal atropine diminished the response of SARs to 10 mug/kg of histamine but had no significant effect on the response of SARs to histamine at 60 mug/kg. All the responses of SARs to histamine were completely blocked by topical application of mequitazine. These results suggest that the change of SAR activity produced by histamine at 10 mug/kg occurs mainly as a result of the release of acethylcholine (ACh) via the vagovagal reflex and that the activation of H-1-receptors of the airway smooth muscle contributes importantly to the response of SARs to histamine at 60 mug/kg.